Xenotransplantation may be a solution to the shortage of organs affecting thousands of people. Xenografts are rejected by several mechanisms and overcoming this problem will allow us to create a limitless source of organs suitable for transplantation with minimal or no rejection. The objective of this proposal is the study of the interactions affecting Natural Killer (NK) cells recognition of other cells. The recognition of "non-self' cells by NK cells is one of the major problems during organ transplantation, especially between different species (xenotransplantations). Overcoming these interactions is one of the key steps necessary for a successful organ transplant. By having a better understanding of the interactions that take place between "self' or "non-self' cells and NK cells, we will have a better chance to create a mechanism that minimizes the rejection of the transplanted organ. We will study these interactions with established NK cell lines and pig cells. The pig cell lines to be used have been modified to regulate the expression of MHC class I proteins and/or expressed certain HLA molecules by means used by viruses during infection of hosts cells. NK cells isolated from whole blood will be also used to study these interactions.